Investigations are being made on the effects of 6 psychotropic agents on brain nuclear ribosomal RNA metabolism. The effects of amphetamine, morphine, delta 9-tetrahydrocannabinol, phenobarbital, chlorpromazine and LSD on brain nuclear ribosomal RNA metabolism are being investigated. Direct homogenization of brain tissue of different subregions in hypertonic sucrose and centrifugation using discontinuous sucrose gradients yield high purified nuclei. Only granular neuronal nuclei and neuronal nuclei can be clearly distinguished by the light microscope. Using various brain subregions, it is difficult to characterize any nuclei as originating from astrocytes, oligodendrocytes or microglia. We feel that many neuronal nuclei containing more than a single nucleolus are misidentified as astrocytic nuclei. Similarly, many nuclei classified as oligodendrocytic are actually granular neurons. We are currently investigating procedures for identification of these nuclei, assay of aggregate RNA polymerase activity and solubilization of RNA polymerase into its different forms. The effects of the psychotropic agents on RNA polymerase activity and stability of nuclear RNA are being studied.